Three-dimensional self-assembled nucleic acid nanoparticles and use thereof

Abstract

The present invention relates to three-dimensional self-assembled nucleic acid nanoparticles, a drug delivery system comprising the same, and a pharmaceutical composition for the prevention or treatment of acute kidney injury, which comprises the same. The three-dimensional self-assembled nucleic acid nanoparticles of the present invention, which have a tetrahedral structure, exhibit an excellent renal-targeting ability, and thus the nanoparticles conjugated with the pharmaceutically active ingredient for p53 exhibit excellent p53 and caspase 3 expression reductions in vitro and in vivo, and can thereby be applied to the prevention or treatment of acute kidney injury.

The invention claimed is: 
     
       1. A kidney-specific drug delivery system comprising three-dimensional self-assembled nucleic acid nanoparticles having a tetrahedral structure, wherein the nucleic acid nanoparticles consist of one or more oligonucleotides selected from the group consisting of SEQ ID Nos: 1 to 4. 
     
     
       2. The kidney-specific drug delivery system of  claim 1 , wherein the oligonucleotide consists of any one selected from the group consisting of D-DNA, L-DNA, 2′-fluoro-RNA, and 2′-O-methoxy-RNA. 
     
     
       3. The kidney-specific drug delivery system of  claim 1 , wherein the oligonucleotide consisting of the nucleotide sequence of SEQ ID NOs: 1 to 4 consists of any one of 2′-fluoro-RNA and 2′-O-methoxy-RNA. 
     
     
       4. The kidney-specific drug delivery system of  claim 1 , wherein a number of the oligonucleotides forming the nucleic acid nanoparticles is four. 
     
     
       5. The kidney-specific drug delivery system of  claim 1 , wherein the nucleic acid nanoparticles comprise a double-stranded nucleic acid including a hybridization region in which the oligonucleotide and the oligonucleotide hybridizing thereto are hybridized, wherein the double-stranded nucleic acid forms a side of a surface of a nucleic acid nanoparticle structure. 
     
     
       6. The kidney-specific drug delivery system of  claim 1 , wherein the drug delivery system further comprises a pharmaceutically active ingredient. 
     
     
       7. A pharmaceutical composition, comprising:
 a kidney-specific drug delivery system of  claim 1 ; and 
 a pharmaceutically active ingredient bound to the drug delivery system. 
 
     
     
       8. The pharmaceutical composition of  claim 7 , wherein the pharmaceutical composition comprises:
 a first oligonucleotide including D-DNA or L-DNA bound to the 3′ end of any one of four oligonucleotides forming the three-dimensional self-assembled nucleic acid nanoparticles of the drug delivery system; 
 a second oligonucleotide hybridized to the first oligonucleotide to form a duplex; and 
 a pharmaceutically active ingredient linked to the second oligonucleotide forming the duplex. 
 
     
     
       9. The pharmaceutical composition of  claim 7 , wherein the pharmaceutically active ingredient inhibits a gene upregulating an apoptosis pathway. 
     
     
       10. The pharmaceutical composition of  claim 9 , wherein the gene upregulating an apoptosis pathway is any one or more selected from the group consisting of p53, Fas, a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a tumor necrosis factor (TNF), receptors thereof, bcl-2 and caspase. 
     
     
       11. The pharmaceutical composition of  claim 10 , wherein the gene is p53. 
     
     
       12. The pharmaceutical composition of  claim 7 , wherein the pharmaceutically active ingredient is any one or more selected from the group consisting of siRNA, shRNA, an antisense oligonucleotide, and microRNA.